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Carvacrol has demonstrated antioxidant activity; however, its high volatility and low water solubility limit its direct application in food matrices. Then, an effective encapsulation system is required to protect it. This study aimed to design and characterize a carvacrol-based additive encapsulated in a spray-dried multilayer emulsion based on chitosan/sodium alginate/maltodextrin. Spray-drying temperature of 120 °C and 3 %(w/w) maltodextrin content maximized both encapsulation efficiency (~97 %) and loading capacity (~53 %). The powder's antioxidant properties were evaluated in two food simulant media: water (SiW) and water-ethanol (SiD). The highest antioxidant activity was observed in SiW for both ABTSâ¢+ (8.2 ± 0.3mgEAG/g) and FRAP (4.1 ± 0.2mgEAG/g) methods because of the reduced release of carvacrol in SiD vs. SiW, as supported by micro- and macrostructural observations by SAXS and microscopy, respectively. An increase from 143 to 157 °C attributable to carvacrol protection and Tg = 44.4 °C (> ambient) were obtained by TGA and DSC, respectively. FT-IR confirmed intermolecular interactions (e.g. -COO- and -NH3+) as well as H-bonding formation. High water solubility (81 ± 3 %), low hygroscopicity (8.8 ± 0.2 %(w/w), poor flowability (CI:45 ± 4), and high cohesiveness (HR:1.8 ± 0.1) between particles were achieved, leading to a powdered antioxidant additive with high potential for applications which required avoiding/reducing oxidation on hydrophilic and hydrophobic food products.
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Alginatos , Antioxidantes , Quitosano , Cimenos , Emulsiones , Polisacáridos , Polvos , Quitosano/química , Antioxidantes/química , Antioxidantes/farmacología , Cimenos/química , Alginatos/química , Emulsiones/química , Polisacáridos/química , Ácido Glucurónico/química , Ácidos Hexurónicos/químicaRESUMEN
PURPOSE: Although the mechanical properties of paracetamol and MCC are extensively described in literature, there still is a need for a better understanding of the material properties impacting them. Thus, this study systematically analyzed material properties of paracetamol-MCC blends to elucidate their influence on the mechanical tablet properties in roller compaction and direct compression with special focus on surface properties. METHODS: Multiple material characteristics of binary mixtures of paracetamol and MCC with varying drug loads were analyzed, with particular emphasis on specific surface area and surface energy. Subsequently, mechanical tablet properties of the materials in direct compression and after roller compaction were examined. RESULTS: It was demonstrated that the impact of the initial material properties on mechanical tablet properties prevailed over the impact of processing route for paracetamol-MCC blends, underlining the importance of material characterization for tabletability of oral solid dosage forms. By applying bivariate as well as multivariate analysis, key material properties influencing the tabletability of paracetamol, MCC and its mixtures such as surface area, surface energy, effective angle of internal friction and density descriptors were identified. CONCLUSIONS: This study highlighted the importance of comprehensive assessment of different material characteristics leading to a deeper understanding of underlying factors impacting mechanical tablet properties in direct compression and after roller compaction by the example of paracetamol-MCC mixtures with varying drug loads. Furthermore, it was shown that multivariate analysis could be a valuable extension to common bivariate analysis to reveal underlying correlations of material properties.
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Acetaminofén , Excipientes , Composición de Medicamentos , Comprimidos , Presión , Polvos , Resistencia a la Tracción , Tamaño de la PartículaRESUMEN
During the development of an oral solid form of a drug substance, a thorough understanding of the critical material attributes is necessary, as the physical properties of the active pharmaceutical ingredient (API) can profoundly influence the drug product's manufacturability, critical quality attributes, and bioavailability. The objective of this study was to validate the manufacturing process of the drug Linezolid from three different sources at both the pilot and industrial scale and to identify differences in critical material attributes between the API manufacturers. Furthermore, the scalability factor between the pilot and industrial scale and the suitability of a process for direct compression were also evaluated. In the present study, the different sources of API were characterized by SeDeM methodology, particle size distribution, and scanning electron microscopy determinations. The statistical analysis revealed that no statistically significant differences were found for any of the parameters under study for the same API source analyzed on both scales. On the other hand, for most of the parameters evaluated, statistical differences were observed between the different sources. It was concluded that SeDeM was able to successfully validate the API manufacturing process, assess scalability, and distinguish between sources. Therefore, it could be highly valuable in the formulation phase to select the best API source.
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Particulate amorphous solid dispersions (ASDs) have been recognised for their potential to enhance the performance of various solid dose forms, especially oral bioavailability and macromolecule stability. However, the inherent nature of spray-dried ASDs leads to their surface cohesion/adhesion, including hygroscopicity, which hinders their bulk flow and affects their utility and viability in terms of powder production, processing, and function. This study explores the effectiveness of L-leucine (L-leu) coprocessing in modifying the particle surface of ASD-forming materials. Various contrasting prototype coprocessed ASD excipients from both the food and pharmaceutical industries were examined for their effective coformulation with L-leu. The model/prototype materials included maltodextrin, polyvinylpyrrolidone (PVP K10 and K90), trehalose, gum arabic, and hydroxypropyl methylcellulose (HPMC E5LV and K100M). The spray-drying conditions were set such that the particle size difference was minimised, so that it did not play a substantial role in influencing powder cohesion. Scanning electron microscopy was used to evaluate the morphology of each formulation. A combination of previously reported morphological progression typical of L-leu surface modification and previously unreported physical characteristics was observed. The bulk characteristics of these powders were assessed using a powder rheometer to evaluate their flowability under confined and unconfined stresses, flow rate sensitivities, and compactability. The data showed a general improvement in maltodextrin, PVP K10, trehalose and gum arabic flowability measures as L-leu concentrations increased. In contrast, PVP K90 and HPMC formulations experienced unique challenges that provided insight into the mechanistic behaviour of L-leu. Therefore, this study recommends further investigations into the interplay between L-leu and the physico-chemical properties of coformulated excipients in future amorphous powder design. This also revealed the need to enhance bulk characterisation tools to unpack the multifactorial impact of L-leu surface modification.
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The relevance of the polymorphic form, particle size, and processing of mannitol for the mechanical properties of solid oral dosage forms was examined. Thus, particle and powder properties of spray granulated ß D-mannitol, ß D-mannitol, and δ D-mannitol were assessed in this study with regards to their manufacturability. D-mannitol is a commonly used excipient in pharmaceutical formulations, especially in oral solid dosage forms, and can be crystallized as three polymorphic forms, of which ß is the thermodynamically most stable form and δ is a kinetically stabilized polymorph. A systematic analysis of the powders as starting materials and their respective roller compacted granules is presented to elucidate the multidimensional effects of powder and granules characteristics such as polymorphic form, particle size, and preprocessing on the resulting tablets' mechanical properties. In direct compression and after roller compaction, δ polymorph displayed superior tableting properties over ß mannitol, but was outperformed by spray granulated ß mannitol. This could be primarily correlated to the higher specific surface area, leading to higher bonding area and more interparticle bonds within the tablet. Hence, it was shown that surface characteristics and preprocessing can prevail over the impact of polymorphism on manufacturability for oral solid dosage forms.
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Powder materials are used in all corners of materials science, from additive manufacturing to energy storage. Scanning electron microscopy (SEM) has developed to meet morphological, microstructural and bulk chemical powder characterization requirements. These include nanoscale elemental analysis and high-throughput morphological assays. However, spatially localized powder surface chemical information with similar resolution to secondary electron (SE) imaging is not currently available in the SEM. Recently, energy filtered (EF-) SEM has been used for surface chemical characterization by secondary electron hyperspectral imaging (SEHI). This review provides a background to existing powder characterization capabilities in the low voltage SEM provided by SE imaging, EDX analysis and BSE imaging and sets out how these capabilities could be extended for surface chemical analysis by applying SEHI to powders, with particular emphasis on air and beam sensitive powder surfaces. Information accessible by SEHI, its advantages and limitations, is set into the context of other chemical characterization methods that are commonly used for assessing powder surface chemistry such as by Auger electron spectroscopy (AES) and X-ray photoelectron spectroscopy (XPS). The applicability of existing powder preparation methods for SEM to SEHI is also reviewed. An alternative preparation method is presented alongside first examples of SEHI characterization of powder surfaces. The commercial powder materials used as examples were carbon-fiber/polyamide composite powder feedstock (CarbonMide®) used in additive manufacturing and powders consisting of lithium nickel cobalt oxide (NMC). SEHI is shown to differentiate bonding present at carbonaceous material surfaces and extract information about the work function of metal oxide surfaces. The surface sensitivity of SEHI is indicated by comparison of pristine powders to those with surface material added in preparation. A minimum spatial localization of chemical information of 55â¯nm was achieved in differentiating regions of NMC surface chemistry by distinct SE spectra.
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Electrones , Imágenes Hiperespectrales , Microscopía Electrónica de Rastreo , Espectroscopía de Fotoelectrones , Polvos/químicaRESUMEN
In the present study drying of orange pomace was carried out at 50, 60 and 70 °Cand drying kinetics was evaluated. The characterization of the orange pomace powder dried at the three different temperatures was carried out. Modified page model was found to best fit the data on drying, whereas effective moisture diffusivity ranged from 3.34 × 10-10 to 1.06 × 10-9 m2/s and the activation energy obtained was 53.07 kJ/mol. The results from powder characterization showed that the chemical composition, water holding capacity and oil holding capacity were not influenced by temperature. The emulsifying activity, swelling capacity and crystallinity were improved by increasing the temperature of drying. The antioxidant capacity and vitamin C content were observed to decrease with increase in drying temperature. There were no noticeable changes in the functional groups or structure due to temperature.
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Environmental conditions can have a profound impact on the bulk behaviour of pharmaceutical powders, including their tribo-charging tendency. Typically, high relative humidity (RH) has been associated to a reduction in the electrostatic charge of the material. However, the occurrence of charge mitigation seems to be related to the quantity of water molecules at the powder surface, which depends on intrinsic material attributes (i.e., water sorption propensity), and external factors (i.e., RH level). In the present study, pharmaceutical powders (i.e., microcrystalline cellulose, D-mannitol, paracetamol and magnesium stearate) were conditioned at three levels of RH, relevant for pharmaceutical operations, and their bulk behaviour, including charging propensity, was analyzed. Depending on the material type, powders sorbed water from the humid atmosphere to different extents, resulting in different charging behaviours. Overall, the charge density of the materials was found to decrease after a certain RH or monotonically decrease with an increase of RH, except for D-mannitol. For this material, a contrasting trend of increase in charging was observed with an increase in RH. Moreover, the powders showed a distinct tribo-charging sensitivity to RH, with paracetamol being the most affected. These findings suggest that a careful consideration on solid material-moisture interactions is needed when using RH as strategy to minimize electrostatic effects in powder processing.
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Emolientes , Manitol , Humedad , Polvos , Electricidad EstáticaRESUMEN
Powder feeding is a crucial unit operation in continuous manufacturing (CM) of pharmaceutical products. Twin-screw feeders are typically employed to ensure the accurate mass flow of pharmaceutical materials throughout the production process. Here, contact and separation of particles can give rise to electrostatic charges, affecting feeder performance and final product quality. The knowledge of the material charging tendency would therefore be beneficial for both formulation and process design. At the early stage of product development, only a limited amount of material is available and the propensity of the powders to charge needs to be assessed on lab test equipment, which not necessarily represent the material state during processing. In this study, the tribo-charging behaviour of a set of common pharmaceutical materials (i.e., microcrystalline cellulose, D-mannitol, paracetamol and magnesium stearate) was experimentally evaluated. To this end, powder materials were let to flow over the stainless-steel pipes of the GranuCharge™ instrument. The resulting charge was compared to the one acquired during twin-screw feeding. In both cases, paracetamol exhibited the highest charging tendency followed by D-mannitol and microcrystalline cellulose and last by magnesium stearate. A good correlation was found for charge values obtained for both methods, despite the different tribo-charging mechanisms involved in the two set-ups. However, these differences in experimental set-ups led to diverse magnitudes and, in one case, polarity of charge. Additionally, an extensive material characterization was performed on the selected powders and results were statistically analyzed to identify critical material attributes (CMAs) affecting powder tribo-charging. A strong correlation was obtained between the measured charge and inter-particle friction. This indicated the latter as one of the most influencing material characteristic impacting the powder tribo-charging phenomenon of the selected materials.
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Química Farmacéutica , Manitol , Tamaño de la Partícula , Polvos , Electricidad Estática , Tecnología FarmacéuticaRESUMEN
Powders of constant morphology and quality are indispensable for reproducible ceramic manufacturing. In this study, commercially available powders were characterized regarding their microstructural properties and screened for a reproducible membrane manufacturing process, which was done by sequential tape casting. Basing on this, the slurry composition and ratio of ingredients were systematically varied in order to obtain flat, crack-free green tapes suitable for upscaling of the manufacturing process. Debinding and sintering parameters were adjusted to obtain defect-free membranes with diminished bending. The crucial parameters are the heating ramp, sintering temperature, and dwell time. The microstructure of the asymmetric membranes was investigated, leading to a support porosity of approximately 35% and a membrane layer thickness of around 20 µm. Microstructure and oxygen flux are comparable to asymmetric La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) membranes manufactured from custom-made powder, showing an oxygen flux of > 1 mLcm-2min at 900 °C in air/Ar gradient.
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Introduction: Dry powder inhalers (DPIs) are popular for pulmonary drug delivery. Various techniques have been employed to produce inhalation drug particles and improve the delivery efficiency of DPI formulations. Physical stability of these DPI formulations is critical to ensure the delivery of a reproducible dose to the airways over the shelf-life.Areas covered: This review focuses on the impact of solid-state stability on aerosolization performance of DPI drug particles manufactured by powder production approaches and particle-engineering techniques. It also highlights the different analytical tools that can be used to characterize the physical instability originating from production and storage.Expert opinion: A majority of the DPI literature focuses on the effects of physico-chemical properties such as size, morphology, and density on aerosolization. While little has been reported on the physical stability, particularly the stability of engineered drug particles for use in DPIs. Literature data have shown that different particle-engineering methods and storage conditions may cause physical instability of dry powders for inhalation and can significantly change the aerosol performance. A systematic examination of physical instability mechanisms in DPI formulations is necessary during formulation development in order to select the optimum formulation with satisfactory stability. In addition, the use of appropriate characterization tools is critical to detect and understand physical instability during the development of DPI formulations.
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Estabilidad de Medicamentos , Inhaladores de Polvo Seco , Preparaciones Farmacéuticas/administración & dosificación , Polvos/química , Administración por Inhalación , Aerosoles/química , Animales , Sistemas de Liberación de Medicamentos , Humanos , Pulmón/metabolismo , Tamaño de la Partícula , Preparaciones Farmacéuticas/químicaRESUMEN
Preparation and formulation of amorphous solid dispersions (ASDs) are becoming more and more popular in the pharmaceutical field because the dissolution of poorly water-soluble drugs can be effectively improved this way, which can lead to increased bioavailability in many cases. During downstream processing of ASDs, technologists need to keep in mind both traditional challenges and the newest trends. In the last decade, the pharmaceutical industry began to display considerable interest in continuous processing, which can be explained with their potential advantages such as smaller footprint, easier scale-up, and more consistent product, better quality and quality assurance. Continuous downstream processing of drug-loaded ASDs opens new ways for automatic operation. Therefore, the formulation of poorly water-soluble drugs may be more effective and safe. However, developments can be challenging due to the poor flowability and feeding properties of ASDs. Consequently, this review pays special attention to these characteristics since the feeding of the components greatly influences the content uniformity in the final dosage form. The main purpose of this paper is to summarize the most important steps of the possible ASD-based continuous downstream processes in order to give a clear overview of current course lines and future perspectives.
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White horehound (Marrubium vulgare L.), is a grey-leaved perennial herb, belonging to Lamiaceae family, distributed in Eurasia and northern Africa. Despite the fact that M. vulgare has been used since ancient times in treating diverse diseases, it is only in the last decade or so that scientists have been able to lay the foundation for its potential pharmacological actions from the results observed through the prism of ethnopharmacological use of this species. The novelty of this study was that subcritical water extraction, acknowledged as a powerful extraction technology to recover phenolic compounds, was coupled with spray drying. The subcritical horehound extract, obtained using optimal process parameters, was used as a liquid feed in spray drying. Maltodextrin was used as a carrier in a concentration of 10%. Thus, two M. vulgare powders, carrier-free and 10% MD, were produced. Comprehensive powders characterization was conducted in order to evaluate their quality. Results confirmed that spray drying can be used as a method of choice for obtaining high quality horehound powders which kept the amorphous structure constant after 6 months.
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In this work, the aqueous extract obtained from Brazilian ginseng (Pfaffia glomerata) roots (BGR), rich in beta-ecdysone and fructooligosaccharides (FOS), was powdered by spray drying and freeze drying techniques aiming to obtain a novel functional food product. The effects of these drying techniques on the chemical and nutritional quality, morphological and redispersion properties of the BGR powders were evaluated. The BGR powders obtained by both spray drying and freeze drying techniques maintained their beta-ecdysone and FOS contents after drying, demonstrating the stability of these functional compounds. It was found that the wettability of the powders obtained by different treatments was affected by the drying technique because freeze-dried particles reached the lower values (66⯱â¯5â¯s) while spray-dried particles showed a greater time for dispersion into water (150⯱â¯25â¯s). This behavior was mainly associated with differences between powder morphological properties since the freeze-dried particles presented a more porous structure, resulting in a greater water diffusivity into microstructure during the redispersion process. Drying process did not affect the storage stability of powders because the glass transition temperature (Tg) for both samples was approximately 160⯰C at a relative humidity of 56%. Thus, both BGR powders presented adequate redispersion properties to constitute a new functional tea or even to be used as a functional ingredient in food products.
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Bebidas , Ecdisterona/aislamiento & purificación , Manipulación de Alimentos/métodos , Alimentos Funcionales , Valor Nutritivo , Oligosacáridos/aislamiento & purificación , Panax/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Aerosoles , Cristalografía por Rayos X , Liofilización , Tamaño de la Partícula , Polvos , Solubilidad , Temperatura de Transición , Vitrificación , Agua/análisis , HumectabilidadRESUMEN
Intranasal vaccination using dry powder vaccine formulation represents an attractive, non-invasive vaccination modality with better storage stability and added protection at the mucosal surfaces. Herein we report that it is feasible to induce specific mucosal and systemic antibody responses by intranasal immunization with a dry powder vaccine adjuvanted with an insoluble aluminum salt. The dry powder vaccine was prepared by thin-film freeze-drying of a model antigen, ovalbumin, adsorbed on aluminum (oxy)hydroxide as an adjuvant. Special emphasis was placed on the characterization of the dry powder vaccine formulation that can be realistically used in humans by a nasal dry powder delivery device. The vaccine powder was found to have "passable" to "good" flow properties, and the vaccine was uniformly distributed in the dry powder. An in vitro nasal deposition study using nasal casts of adult humans showed that around 90% of the powder was deposited in the nasal cavity. Intranasal immunization of rats with the dry powder vaccine elicited a specific serum antibody response as well as specific IgA responses in the nose and lung secretions of the rats. This study demonstrates the generation of systemic and mucosal immune responses by intranasal immunization using a dry powder vaccine adjuvanted with an aluminum salt.
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Adyuvantes Inmunológicos/administración & dosificación , Hidróxido de Aluminio/administración & dosificación , Óxido de Aluminio/administración & dosificación , Vacunas/administración & dosificación , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/farmacocinética , Administración Intranasal , Hidróxido de Aluminio/química , Hidróxido de Aluminio/farmacocinética , Óxido de Aluminio/química , Óxido de Aluminio/farmacocinética , Animales , Antígenos/administración & dosificación , Antígenos/química , Antígenos/inmunología , Encéfalo/metabolismo , Líquido del Lavado Bronquioalveolar/inmunología , Femenino , Inmunización , Inmunoglobulina A/inmunología , Inmunoglobulina G/sangre , Líquido del Lavado Nasal/inmunología , Ovalbúmina/administración & dosificación , Ovalbúmina/química , Ovalbúmina/inmunología , Polvos , Ratas Sprague-Dawley , Vacunas/química , Vacunas/farmacocinéticaRESUMEN
This study aims to optimize extraction and drying conditions of fig syrup. Drying was done in a pilot scale two-fluid nozzle spray dryer. A total of 27 experiments were conducted with varying inlet air temperatures, air flow rates, and also a maltodextrin (MD)- low methoxyl pectin (LMP) ratios. While feed rate, feed temperature, and compressed air flow rate of the atomizer were kept constant. The results of differential scanning calorimetry revealed that high levels of glucose and fructose in the extract resulted in a low glass transition temperature of fig syrup. By an increase in the inlet air temperature, the powder bulk density decreased. However, the MD:LMP ratio and the air flow rate were not significantly effective (p < 0/05) in changing the bulk density. SEM micrographs of spray-dried particles and particle size distribution analysis showed that particles were largely in a range of 5 to 50 µm. The best powders were obtained at an inlet air temperature of 170°C.
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Characterization of particulate systems (powders) is one of the remaining scientific challenges. Evaluation of powder behaviour is often empirical and the decision-making processes are experience-based. There is a need for development of analytical instrumentation enabling more fundamental understanding of powder behaviour. Flowability and tabletability, two key factors in commercial scale manufacturing of tablets with direct compression (DC) approach, were analysed for formulations containing increasing amounts of several model active pharmaceutical ingredients (APIs). Flowability was investigated using a ring shear tester and tablets were prepared at four different compression pressures using a single punch tablet press. Thereby, a material sparing screening approach was developed to estimate the influence of APIs on behaviour of a given DC formulation. Additionally, this approach is useful for estimating the low threshold amount of API (wt%), at which the properties of an API start affecting the powder behaviour of a given formulation (API-excipient mixture). This threshold will be referred to as critical drug loading. The flowability of microcrystalline cellulose (reference grade pH 102) was used as a threshold for adequate flowability of model formulations. The threshold for tablet tensile strength was set to 2MPa. Simultaneous visual presentation of both- flowability and tabletability were used for a fast evaluation of manufacturability of a given formulation. The results confirmed that flowability is more sensitive to drug loading than tabletability, and that the critical drug loading for a DC formulation is strongly affected by particulate properties of API. For example, decreasing the particle size of paracetamol led to rapid decrease in flowability index, whereas the tabletability was not affected.
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Composición de Medicamentos/métodos , Polvos , Comprimidos , Celulosa , Tamaño de la Partícula , Presión , Reología , Resistencia a la TracciónRESUMEN
The physical properties of both raw materials and excipients are closely correlated with the quality of traditional Chinese medicine preparations in oral solid dosage forms. In this paper, based on the concept of the chemical fingerprint for quality control of traditional Chinese medicine products, the method of physical fingerprint for quality evaluation of traditional Chinese medicine extract powders was proposed. This novel physical fingerprint was built by the radar map, and consisted of five primary indexes (i.e. stackablity, homogeneity, flowability, compressibility and stability) and 12 secondary indexes (i.e. bulk density, tap density, particle size<50 µm percentage, relative homogeneity index, hausner ratio, angle of repose, powder flow time, inter-particle porosity, Carr index, cohesion index, loss on drying, hygroscopicity). Panax notoginseng saponins (PNS) extract was taken for an example. This paper introduced the application of physical fingerprint in the evaluation of source-to-source and batch-to-batch quality consistence of PNS extract powders. Moreover, the physical fingerprint of PNS was built by calculating the index of parameters, the index of parametric profile and the index of good compressibility, in order to successfully predict the compressibility of the PNS extract powder and relevant formulations containing PNS extract powder and conventional pharmaceutical excipients. The results demonstrated that the proposed method could not only provide new insights into the development and process control of traditional Chinese medicine solid dosage forms.
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Medicamentos Herbarios Chinos/normas , Control de Calidad , Composición de Medicamentos , Medicina Tradicional China , Tamaño de la Partícula , Polvos/normasRESUMEN
The physical properties of both raw materials and excipients are closely correlated with the quality of traditional Chinese medicine preparations in oral solid dosage forms. In this paper, based on the concept of the chemical fingerprint for quality control of traditional Chinese medicine products, the method of physical fingerprint for quality evaluation of traditional Chinese medicine extract powders was proposed. This novel physical fingerprint was built by the radar map, and consisted of five primary indexes (i.e. stackablity, homogeneity, flowability, compressibility and stability) and 12 secondary indexes (i.e. bulk density, tap density, particle size<50 μm percentage, relative homogeneity index, hausner ratio, angle of repose, powder flow time, inter-particle porosity, Carr index, cohesion index, loss on drying, hygroscopicity). Panax notoginseng saponins (PNS) extract was taken for an example. This paper introduced the application of physical fingerprint in the evaluation of source-to-source and batch-to-batch quality consistence of PNS extract powders. Moreover, the physical fingerprint of PNS was built by calculating the index of parameters, the index of parametric profile and the index of good compressibility, in order to successfully predict the compressibility of the PNS extract powder and relevant formulations containing PNS extract powder and conventional pharmaceutical excipients. The results demonstrated that the proposed method could not only provide new insights into the development and process control of traditional Chinese medicine solid dosage forms.
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A pregelatinized starch (PGS) was derivatized with sodium chloroacetate (SCA) in alcoholic medium under alkaline condition to produce carboxymethyl pregelatinized starch (CMPGS) with various degrees of substitution (DS). Influence of the molar ratio of SCA to the glucopyranose units (SCA/GU), reaction time, temperature and the amount of sodium hydroxide on the degree of substitution (DS) and the reaction efficiency (RE) was studied. An optimal concentration of 30% of NaOH, for a reaction time of 1 h at 50 °C and molar ratio (SCA/GU) equal to 1.0, yielded an optimal DS of 0.55 and a RE of 55%. SEM micrographs revealed that the carboxymethylation assigned the structural arrangement of CMPGS and caused the granular disintegration. Wide angle diffraction X-ray (XRD) showed that the crystallinity of starch was obviously varied after carboxymethylation. New bands in FTIR spectra at 1417 and 1603 cm(-1) indicated the presence of carboxymethyl groups. The solubility and viscosity of CMPGS increased with an increase in the degree of modification. In order to investigate the influence of DS on physical and drug release properties, CMPGS obtained with DS in the range of 0.12-0.55 was evaluated as tablet excipient for sustained drug release. Dissolution tests performed in phosphate buffer (pH 6.8), with Ibuprofen as drug model (25% loading) showed that CMPGS seems suitable to be used as sustained release excipient since the drug release was driven over a period up to 8 h. The in vitro release kinetics studies revealed that all formulations fit well with Korsmeyer-Peppas model and the mechanism of drug release is non-Fickian diffusion.